Hypercapnic acidosis attenuates ventilation-induced lung injury by a nuclear factor-κB-dependent mechanism.

Objectives: Hypercapnic acidosis protects against ventilation-induced lung injury. We wished to determine whether the beneficial effects of hypercapnic acidosis in reducing stretch-induced injury were mediated via inhibition of nuclear factor-κB, a key transcriptional regulator in inflammation, injury, and repair.

Design: Prospective randomized animal study.

Clinical review: Stem cell therapies for acute lung injury/acute respiratory distress syndrome - hope or hype?

A growing understanding of the complexity of the pathophysiology of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), coupled with advances in stem cell biology, has led to a renewed interest in the therapeutic potential of stem cells for this devastating disease. Mesenchymal stem cells appear closest to clinical translation, given the evidence that they may favourably modulate the immune response to reduce lung injury, while maintaining host immune-competence and also facilitating lung regeneration and repair. The demonstration that human mesenchymal stem cells exert benefit in the endotoxin-injured human lung is particularly persuasive.

Hypercapnia induces cleavage and nuclear localization of RelB protein, giving insight into CO2 sensing and signaling.

Carbon dioxide (CO(2)) is increasingly being appreciated as an intracellular signaling molecule that affects inflammatory and immune responses. Elevated arterial CO(2) (hypercapnia) is encountered in a range of clinical conditions, including chronic obstructive pulmonary disease, and as a consequence of therapeutic ventilation in acute respiratory distress syndrome. In patients suffering from this syndrome, therapeutic hypoventilation strategy designed to reduce mechanical damage to the lungs is accompanied by systemic hypercapnia and associated acidosis, which are associated with improved patient outcome.

Studies on the pathogenesis and survival of different culture forms of Listeria monocytogenes to pulsed UV-light irradiation after exposure to mild-food processing stresses.

The effects of mild conventional food-processing conditions on Listeria monocytogenes survival to pulsed UV (PUV) irradiation and virulence-associated characteristics were investigated. Specifically, this study describes the inability of 10 strains representative of 3 different culture forms or morphotypes of L. monocytogenes to adapt to normally lethal levels of PUV-irradiation after exposure to sub-lethal concentrations of salt (7.

Mesenchymal stem cells - a promising therapy for Acute Respiratory Distress Syndrome.

Acute Respiratory Distress Syndrome (ARDS) constitutes a spectrum of severe acute respiratory failure in response to a variety of inciting stimuli that is the leading cause of death and disability in the critically ill. Despite decades of research, there are no therapies for ARDS, and management remains supportive. A growing understanding of the complexity of the pathophysiology of ARDS, coupled with advances in stem cell biology, has lead to a renewed interest in the therapeutic potential of mesenchymal stem cells for ARDS.

Mesenchymal stem cells enhance recovery and repair following ventilator-induced lung injury in the rat.

Background: Bone-marrow derived mesenchymal stem cells (MSCs) reduce the severity of evolving acute lung injury (ALI), but their ability to repair the injured lung is not clear. A study was undertaken to determine the potential for MSCs to enhance repair after ventilator-induced lung injury (VILI) and elucidate the mechanisms underlying these effects.

Methods: Anaesthetised rats underwent injurious ventilation which produced severe ALI.

Lung stem cells--from an evolving understanding to a paradigm shift?

The ideal cell type to regenerate an acutely injured or chronically diseased lung would be a stem cell population from the patient's own lung. Consequently, extensive research efforts have focused on identifying and characterizing endogenous lung stem cells. Advances in techniques to facilitate cell isolation, labelling and tracking in vivo to determine their fate have led to the identification of several putative stem cell niches.

Evolution of the inflammatory and fibroproliferative responses during resolution and repair after ventilator-induced lung injury in the rat.

Background: The time course and mechanisms of resolution and repair, and the potential for fibrosis following ventilation-induced lung injury (VILI), are unclear. We sought to examine the pattern of inflammation, injury, repair, and fibrosis following VILI.

Methods: Sixty anesthetized rats were subject to high-stretch; low-stretch, or sham ventilation, and randomly allocated to undergo periods of recovery of 6, 24, 48, and 96 h, and 7 and 14 days.

Clinical review: Special populations--critical illness and pregnancy.

Critical illness is an uncommon but potentially devastating complication of pregnancy. The majority of pregnancy-related critical care admissions occur postpartum. Antenatally, the pregnant patient is more likely to be admitted with diseases non-specific to pregnancy, such as pneumonia.

Overexpression of pulmonary extracellular superoxide dismutase attenuates endotoxin-induced acute lung injury.

Purpose: Superoxide is produced by activated neutrophils during the inflammatory response to stimuli such as endotoxin, can directly or indirectly injure host cells, and has been implicated in the pathogenesis of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). We wished to determine the potential for pulmonary overexpression of the extracellular isoform of superoxide dismutase (EC-SOD) to reduce the severity of endotoxin-induced lung injury.

Methods: Animals were randomly allocated to undergo intratracheal instillation of (1) surfactant alone (vehicle); (2) adeno-associated virus (AAV) vectors containing a null transgene (AAV-null); and (3) adeno-associated virus vectors containing the EC-SOD transgene (AAV-EC-SOD) and endotoxin was subsequently administered intratracheally.

Clinical review: gene-based therapies for ALI/ARDS: where are we now?

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) confer substantial morbidity and mortality, and have no specific therapy. The accessibility of the distal lung epithelium via the airway route, and the relatively transient nature of ALI/ARDS, suggest that the disease may be amenable to gene-based therapies. Ongoing advances in our understanding of the pathophysiology of ALI/ARDS have revealed multiple therapeutic targets for gene-based approaches.

Studies on the relationship between pulsed UV light irradiation and the simultaneous occurrence of molecular and cellular damage in clinically-relevant Candida albicans.

This constitutes the first study to report on the relationship between pulsed UV light (PL) irradiation and the simultaneous occurrence of molecular and cellular damage in clinical strains of Candida albicans. Microbial protein leakage and propidium iodide (PI) uptake assays demonstrated significant increases in cell membrane permeability in PL-treated yeast that depended on the amount of UV pulses applied. This finding correlated well with the measurement of increased levels of lipid hydroperoxidation in the cell membrane of PL-treated yeast.

Ipsilateral transversus abdominis plane block provides effective analgesia after appendectomy in children: a randomized controlled trial.

Background: The transversus abdominis plane (TAP) block provides effective postoperative analgesia in adults undergoing major abdominal surgery. Its efficacy in children remains unclear, with no randomized clinical trials in this population. In this study, we evaluated its analgesic efficacy over the first 48 postoperative hours after appendectomy performed through an open abdominal incision, in a randomized, controlled, double-blind clinical trial.

Bench-to-bedside review: carbon dioxide.

Carbon dioxide is a waste product of aerobic cellular respiration in all aerobic life forms. PaCO2 represents the balance between the carbon dioxide produced and that eliminated. Hypocapnia remains a common - and generally underappreciated - component of many disease states, including early asthma, high-altitude pulmonary edema, and acute lung injury.

Hypocapnia and the injured brain: more harm than benefit.

Objectives: Hypocapnia is used in the management of acute brain injury and may be life-saving in specific circumstances, but it can produce neuronal ischemia and injury, potentially worsening outcome. This review re-examines the rationale for the use of hypocapnia in acute brain injury and evaluates the evidence for therapeutic and deleterious effects in this context.

Data Sources And Study Selection: A MEDLINE/PubMed search from 1966 to August 1, 2009, was conducted using the search terms "hyperventilation," "hypocapnia," "alkalosis," "carbon dioxide," "brain," "lung," and "myocardium," alone and in combination.

Hypercapnia and acidosis in sepsis: a double-edged sword?

Acute respiratory distress syndrome is a devastating disease that causes substantial morbidity and mortality. Mechanical ventilation can worsen lung injury, whereas ventilatory strategies that reduce lung stretch, resulting in a "permissive" hypercapnic acidosis (HCA), improve outcome. HCA directly reduces nonsepsis-induced lung injury in preclinical models and, therefore, has therapeutic potential in these patients.

Differential effects of buffered hypercapnia versus hypercapnic acidosis on shock and lung injury induced by systemic sepsis.

Background: Acute hypercapnic acidosis protects against lung injury caused by nonseptic insults and after both pulmonary and systemic sepsis. The authors wished to dissect the contribution of the acidosis versus hypercapnia per se to the effects of hypercapnic acidosis on the hemodynamic profile and severity of lung injury induced by systemic sepsis.

Methods: In the hypercapnic acidosis series, adult male Sprague-Dawley rats were randomized to normocapnia or hypercapnic acidosis-produced by adding 5% carbon dioxide to the inspired gas-and cecal ligation and puncture performed.

Infection-induced lung injury is worsened after renal buffering of hypercapnic acidosis.

Objective: Prolonged hypercapnia is commonly encountered during the treatment of acute respiratory distress syndrome and acute respiratory failure attributable to other causes with protective ventilation strategies. In these circumstances, compensatory renal buffering returns pH to normal establishing a condition of buffered hypercapnia. It is also common intensive care practice to correct the pH more rapidly using bicarbonate infusions.

A comparison of the Glidescope, Pentax AWS, and Macintosh laryngoscopes when used by novice personnel: a manikin study.

Purpose: Direct laryngoscopic tracheal intubation is a potentially lifesaving procedure, but a difficult skill to acquire and maintain. The consequences of poorly performed intubation attempts are potentially severe. The Pentax AWS and the Glidescope are indirect laryngoscopes that may require less skill to use.

Hypercapnic acidosis attenuates shock and lung injury in early and prolonged systemic sepsis.

Objective: To investigate whether acute hypercapnic acidosis--induced by adding CO2 to inspired gas--would protect against severe systemic sepsis-induced lung and systemic organ injury resulting from cecal ligation and puncture. Acute hypercapnic acidosis protects against lung injury after both nonseptic and early pneumonia-induced lung injury. In contrast, prolonged hypercapnia worsens pneumonia-induced lung injury.